CHAPTER 34. PRURITUS
Carol L. Scot
Because of the overall low prevalence of pruritus in the palliative care population, pruritus is not always included in the list of distressing symptoms to be addressed with palliation, but its relief matters greatly to the few people who have it. Severe pruritus can destroy sleep and diminish quality of life.
DEFINITION AND INCIDENCE
Pruritus, or itching, is the unpleasant sensation that provokes an urge to scratch. It generally involves a complex series of interactions among the skin, inflammatory processes, cutaneous nerves, and the central nervous system (Fleischer, 2000). Because minor or short-lived itching episodes rarely come to medical notice, the incidence of itching in the general population is not known. The lifetime experience of itching probably approaches 100%.
Researchers have attempted to assess the incidence and prevalence of itching in some subsets of patients. Pruritus occurs in about 30% of patients with psoriasis (Levine & Levine, 2004). Approximately 50% to 70% of patients with primary biliary cirrhosis experience pruritus (Talwalkar, Souto, Jorgensen et al., 2003). The fact that intractable pruritus can be an indication for liver transplantation demonstrates how severely pruritus can affect the quality of a person’s life (Terg, Coronel, Sorda et al., 2002). The prevalence of renal itch among patients on dialysis is estimated to be between 22% and 48% (Manenti, Vaglio, Costantino et al., 2005). In survivors of severe burns, the incidence of pruritus is as high as 87% (Field, Peck, Hernandez-Reif et al., 2000).
Even though much of the physiological basis of pruritus has been described, it is not completely understood, with the consequence that no specific antipruritic drug is available. “This is particularly unfortunate as, although itching is popularly perceived as a minor social or even humorous disability, it is frequently so severe and intractable as to cause the sufferer abject misery or even suicidal inclination” (Greaves & Wall, 1999, p. 487).
When itching is a major symptom in patients with far-advanced illness, all efforts need to be made to alleviate the discomfort, whether or not a precise cause is known.
ETIOLOGY AND PATHOPHYSIOLOGY
The sensation of itching appears to be the same in conditions as diverse as renal failure, insect bites, fungal infections, lymphoma, dry skin, liver failure, multiple sclerosis, and healing wounds, yet its pathophysiology in these conditions is not all the same, and treatments that work for some fail for others.
Itch can be cutaneous, neuropathic, neurogenic, mixed, or psychogenic.
In the skin, unmyelinated nerve fibers—C-fibers—mediate both cutaneous itch and pain. The C-fibers that mediate cutaneous itch cannot be differentiated anatomically from the ones that mediate pain, but they can be differentiated functionally (Fleischer, 2000; Twycross, Greaves, Handwerker et al., 2003). “The afferent C-fibres subserving this type of itch are a functionally distinct subset: they respond to histamine, acetylcholine and other pruritogens, but are insensitive to mechanical stimuli” (Twycross et al., 2003, p. 8).
Such C-fibers comprise about 5% of the C-fibers in human skin. Differentiation of the sensations of pain and itch may also depend on the specific anatomy and physiology of the person experiencing it. Acetylcholine causes itching in the skin of atopic patients, but when it is injected into the skin of nonatopic persons, it causes pain (Twycross et al., 2003).
Another similarity in the physiology of pain and itch is the phenomenon of severe pain or pruritus sensitizing an area around it. With pain, this is called allodynia, in which the skin interprets benign touch as pain. The area around an intensely pruritic area can similarly be sensitized to interpret light touch as intense itch (allokinesis) (Twycross et al., 2003).
Histamine plays a primary role in the pruritus of many commonly occurring itchy conditions such as insect bites, drug reactions, urticaria, and wound healing, but not in other conditions. Histamine receptors H 1 and H 2 are found in the skin.
Serotonin is less pruritogenic in the skin than histamine, but in some types of itch, such as cholestasis-related itching, it seems to play a major role (Fleischer, 2000). Serotonin can cause itch via both peripheral and central mechanisms. In the skin, it releases histamine from mast cells. The central mechanism is inferred because ondansetron (Zofran), a specific 5-HT 3 receptor antagonist, relieves the itch associated with exogenous opioids, and no 5-HT 3 receptors have been found in the skin (Twycross et al., 2003).
Many other naturally occurring chemicals cause local itch when injected into the skin. These include amines, proteases, growth factors, neuropeptides, opioids, eicosanoids, and cytokines. Some produce itch by causing histamine release from mast cells and/or by sensitizing C-fibers. Some stimulate the nerve endings directly (Twycross et al., 2003).
Neuropathic itch can originate from damage to the nervous system, such as with postherpetic neuralgia, notalgia paresthetica (nerve entrapment of spinal nerve roots), and HIV infection. Paroxysmal itch can occur in multiple sclerosis, whereas unilateral pruritus occurs in brain damage, such as with tumors, infections, or stroke (Twycross et al., 2003).
Neurogenic itch is induced centrally without nerve damage and is associated with increased endogenous or exogenous opioids.
Psychogenic itching is a diagnosis of exclusion when itching occurs in association with neuropsychiatric disease and other causes of itching have been ruled out. No systemic disease is found, and no primary skin lesions are found. Secondary lesions of excoriations and lichenification are found on the parts of the body that can be reached by the fingernails, usually sparing the upper back. Some patients deny they scratch despite witnessed scratching and bleeding excoriations (Fleischer, 2000).
CONDITIONS AND MECHANISMS OF ITCHING
Localized
Atopic eczema (or atopic dermatitis) results from an abnormality of T helper type 2 cells resulting in increased transepidermal water loss. Patients usually have had this condition intermittently all their lives. They often have other atopic conditions such as asthma or hayfever and a family history of atopy (Levine & Levine, 2004).
With bites and infestations, scabies, chiggers, lice, and fleas release histamine into the skin.
Brachioradial pruritus is one of the rare forms of persistent localized itching in normal skin, occurring on the lateral aspect of the arms. It occurs most commonly in fair-skinned persons with significant sun exposure but has also had nerve root damage suggested as a cause (Bueller, Bernhard, & Dubroff, 1999; Winhoven, Coulson & Bottomley, 2004).
Burn pruritus is a frequently reported complication in burn survivors, persisting past the active healing phase. It is believed to be mediated by persistent increased mast cells and histamine release (Hettrick, O’Brien, Laznick et al., 2004).
Contact dermatitis (dermatitis venenata; contact eczema) is caused by irritants, which are substances that can damage cells in anyone if given enough exposure (e.g., soaps), or by a type IV hypersensitivity reaction affecting only sensitized persons. Other variants are contact urticarial, which may be immunological, and photocontact variant, where light transforms substances into irritants or antigens (Levine & Levine, 2004).
Fungal infection with Candida albicans causes candidiasis (moniliasis) of the mouth, vagina, skin, and nails, and in immunocompromised persons, it can cause infections of the esophagus, lungs, and blood (Hall, 2000). Tinea pedis is usually caused by Epidermophyton floccosum, Tricophyton rubrum, or T. mentagrophytes. Tinea cruris has the same causative agents as tinea pedis.
“Virtually anything that itches may create a self-perpetuating itch-scratch cycle” (Fleischer, 2000, p. 90). Lichen simplex chronicus (localized neurodermatitis, lichenified dermatitis) and prurigo nodularis are forms of neurodermatitis. “To understand the importance of lichenification and the symptoms which make patients scratch or rub repeatedly, the reader must understand that it takes over 100,000 scratches to make significant lichenification” (Fleischer, 2000, p. 89).
Nummular eczema (nummular dermatitis; discoid eczema) is associated with xerosis, atopy, and venous stasis.
Pruritus ani is an embarrassing proctologic condition affecting about 5% of the population, characterized by intense itching localized in the anus and perianal skin. Local irritants and psychosomatic factors have been suggested as causes but not proved to be of relevance (Lysy, Sistiery-Ittah, Israelit et al., 2003). Urticaria (hives) are caused by allergic and nonallergic mechanisms, with the final common pathway consisting of histamine and other mediator release from mast cells (Levine & Levine, 2004).
Generalized
“It can be stated almost without exception that any drug systemically administered is capable of causing a skin eruption” (Hall, 2000, p. 82). Enteral or parenteral drugs must always be suspected in a generalized skin eruption.
Essential pruritus is the rarest form of generalized pruritus, and is a diagnosis of exclusion only after drug reactions, uremia, malignancy, liver disease, bullous pemphigoid, AIDS, and intestinal parasites have been ruled out (Hall, 2000).
Liver diseases may precipitate pruritus, especially those with cholestasis. Pruritus occurs in approximately 50% to 70% of patients with primary biliary cirrhosis (Talwalkar et al., 2003).
Itching may occur with any malignancy, and the etiology of paraneoplastic itching is poorly understood. Peripheral T-cell lymphoma and other cutaneous lymphomas are notoriously pruritic. Itch has the highest reported prevalence in Hodgkin’s disease, at 10% to 30% (Fleischer, 2000).
Psoriasis occurs most commonly on the scalp, elbows, and the knees but can occur anywhere. The condition is marked by increased proliferation of epidermal keratinocytes associated with an infiltrate of neutrophils and lymphocytes. Erythematous papulosquamous lesions vary in size and shape and usually have a thick, silvery scale. About 30% of these patients itch (Hall, 2000).
Senile pruritus of the elderly occurs year round, mostly in the scalp, shoulders, sacral areas, and the legs and not necessarily associated with dry skin. It may involve a disorder of keratinization (Hall, 2000).
Uremic pruritus is most often paroxysmal, frequently affecting the forearms and back. It may involve unidentified pruritogenic substances accumulating in dialysis patients as a result of molecular size; other theories implicate xerosis, hyperparathyroidism, hypercalcemia, hyperphosphatemia, elevated plasma histamine levels, and uremic neuropathy (Levine & Levine, 2004). The confusion of etiology can be seen in the statements of other reviewers, who state that for the last 20 years various causes of the pruritus of uremia have been explored, and promising mechanisms have been found to be undependable. Some primary culprits of causation have been touted and eliminated, including excessive parathyroid hormone and calcium phosphate crystals. And “it remains to be established whether the opioidergic system plays a significant role in the pathophysiology of uraemic pruritus” (Mettang, Pauli-Magnus & Alscher, 2002, p. 1561).
Water-induced itching or aquagenic pruritus is pruritus that occurs after contact with water or with sudden temperature changes. It may occur alone or in conjunction with polycythemia vera. Aquagenic pruritus is characterized by itching with a pricking sensation that lasts 15 to 60 minutes. Elevated histamine levels are found in the skin during attacks (Fleischer, 2000; Levine & Levine, 2004).
Winter pruritus (pruritus hiemalis) is most common in the elderly and most prominent on the legs and is due to low humidity in heated air (Hall, 2000).
ASSESSMENT AND MEASUREMENT
Like pain, pruritus is by definition an unmeasurable, subjective sensation. If the itch occurs in conjunction with an observable skin condition, the skin abnormality can be described and measured. But the pruritus itself must be reported by the patient or, if not reported, inferred from a patient’s scratching behavior. Most advanced practice nurses assess a patient’s degree of pruritus by the patient’s report that the itch is minor, moderate, or “driving me crazy.”
In a typical pruritus research study, subjects kept a weekly diary, quantifying the amount of itch they were experiencing and their overall well-being on 5-point scales (Browning, Combes & Mayo, 2003). Another commonly used research tool is the visual analogue scale consisting of a 10-cm line marked 0 (no itch) at one end and 10 (maximum itch) at the other end. This is used to measure pruritus at one point in time (Manenti et al., 2005).
Itch in Normal Skin
Itch occurring without visible abnormalities of the skin is usually generalized. The scratching associated with generalized itch can produce the secondary lesions of excoriations.
For patients already known to have conditions that cause generalized pruritus (e.g., malignancy, renal failure, or cholestatic liver disease), efforts can move directly to treatment for relief.
Whether patients with generalized itch who do not have a probable cause will be subjected to an intense search for occult disease or treated empirically depends on the functional status of the patient and his or her desires.
Itch with Localized Abnormality of the Skin
When pruritus is associated with abnormalities of the skin, the abnormality should be carefully assessed and described. The size of the afflicted area, the types of lesions, and their distribution should all be noted.
A short review of the proper terms and descriptions for primary and secondary lesions of the skin follows (Hall, 2000).
Primary and secondary lesions of the skin often occur together in itchy conditions. Secondary lesions may obscure distinctive primary lesions, but a careful examination usually identifies both the primary and the secondary lesions.
Primary Skin Lesions
▪ Macules range up to 1 cm and are round, flat discolorations of the skin.
▪ Patches are larger than 1 cm, flat discolorations of the skin, like vitiligo and senile freckles.
▪ Papules range up to 1 cm in size and are circumscribed elevated superficial solid lesions. A wheal is a type of papule that is edematous and transitory (present less than 24 hours), like hives and some insect bites.
▪ Plaques are larger than 1 cm and are circumscribed, elevated, superficial, solid lesions.
▪ Nodules range up to 1 cm and are solid lesions with depth; they may be above, level with, or beneath the skin surface.
▪ Vesicles range up to 1 cm and are circumscribed elevations of the skin containing serous fluid.
▪ Bullae are larger than 1 cm and are circumscribed elevations that containing serous fluid (e.g., pemphigoid, second-degree burns).
▪ Pustules vary in size and are circumscribed elevations of the skin that contain purulent fluid.
▪ Petechiae range to 1 cm and are circumscribed deposits of blood or blood pigments in the skin.
▪ Purpura is larger than 1 cm and is a circumscribed deposit of blood or blood pigments in the skin.
▪ Burrows are tunnels in the epidermis caused by insects or larvae, such as in scabies or cutaneous larva migrans.
Secondary Skin Lesions
▪ Scales are shedding dead epidermal cells that may be dry (e.g., psoriasis) or greasy (e.g., dandruff).
▪ Crusts are variously colored masses of skin exudates such as seen in impetigo or infected dermatitis.
▪ Excoriations are abrasions of the skin, usually superficial and traumatic.
▪ Fissures are linear breaks in the skin, sharply defined with abrupt walls.
▪ Ulcers are irregularly sized and shaped excavations of the skin extending into the dermis or deeper.
▪ Scars are formations of connective tissue replacing tissue lost through injury or disease.
▪ Keloids are hypertrophic scars beyond the borders of the original injury.
▪ Lichenification is a diffuse area of thickening and scaling with resultant increase in the skin lines and markings (Hall, 2000, pp. 14-17).
HISTORY AND PHYSICAL EXAMINATION
History
In the ideal medical interview, the patient describes his or her symptoms freely and spontaneously and stops when what needs to be communicated has been expressed. The clinician then repeats any information that needs clarification and asks any indicated further questions. When the current problems have been discussed, the clinician then asks questions to uncover any additional problems.
A person suffering from itch may fail to communicate that fact. A patient with intermittent itch may forget to mention it, and even a patient with constant itch may put it out of mind to discuss more urgent matters. If a patient is observed scratching, questions about itch obviously need to be asked. For others, the symptom of itch may be uncovered with general dermatologic questions: Any skin problems? Any lumps, bumps, rashes, itching?
When any symptom, such as itch, is positive, it needs to be further characterized. Has this been a lifelong problem, a recurrent one, or a new one? If new, when did it start? Is the itching localized or general, constant or intermittent? When does it occur (if intermittent), or when is it worst (if constant)? (For a patient who is bothered by itch only at night, morning treatment is unnecessary.) What makes it better; what makes it worse? What treatments have been tried, and with what effect?
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